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Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

At least 595 records · Page 33Linked to original sources

Requirement of donor-derived stromal cells in the bone marrow for successful allogeneic bone marrow transplantation. Complete prevention of recurrence of autoimmune diseases in MRL/MP-Ipr/Ipr mice by transplantation of bone marrow plus bones (stromal cells) from the same donor.

MRL/MP-Ipr/Ipr (MRL/Ipr) mice possess radioresistant (9.5 Gy) abnormal stem cells and show a recurrence of autoimmune diseases within 5 mo of conventional allogeneic bone marrow transplantation. We recently have found that the MHC preference exists between hemopoietic stem cells and stromal cells; when bones are engrafted, donor-derived stromal cells present in the engrafted bones can migrate into the recipient bone marrows, which are replaced with both donor-derived stromal cells and hematopoietic cells. Based on these findings, we attempted to prevent the recurrence of autoimmune diseases in MRL/Ipr mice by the transplantation of both bone marrow cells and bone (as a source of stromal cells). MRL/Ipr mice were irradiated (8.5 Gy) and then reconstituted with C57BL/6 bone marrow cells plus bone grafts. The mice survived more than 48 wk after this treatment. Immunohistologic studies revealed that the mice were completely free from both lymphadenopathy and autoimmune diseases such as lupus nephritis and rheumatoid arthritis. Sera from these mice showed normal levels of circulating immune complexes and rheumatoid factors. Normal functions of both T cells and B cells were noted. Abnormal T cells such as Thy-1+B220+ cells present in nontreated MRL/Ipr mice could not be seen in the thus-treated mice. In addition, to our surprise, spleen cells from treated mice showed completely normal in vitro primary anti-SRBC responses. These results indicate that stromal cells in allogeneic bone marrow transplantation play a crucial role not only in the prevention of graft failure but also in the successful cooperation among APCs, T cells, and B cells. Although MRL/Ipr mice are radiosensitive and usually die of interstitial pneumonia or fatty liver due to the side effects of radiation, it should be noted that this strategy allows a reduction in the radiation dose (9.5 Gy-->8.5 Gy), and that these mice can survive more than 48 wk without showing any symptoms of autoimmune diseases.

Animals↗

[Usefulness of 3DFT-FISP MR imaging in differential diagnosis of liver tumor].

Dynamic 3-dimensional Fourier transformation (3 DFT)-FISP MR imaging was performed in 30 patients with 49 liver tumors (hepatocellular carcinoma 26, hemangioma 13, cholangiocellular carcinoma 2, metastatic liver tumor 8) to evaluate characteristic enhancement patterns. MR images of 3 DFT-FISP (TR/TE/flip angle/slab thickness/partition/slice thickness, 20 msec/8 msec/30 degree/21-75 mm/7 or 15/3-5 mm) were obtained before, just after (early phase), 1 min after (late phase 1) and 2-4 min after (late phase 2) the administration of 0.1 mmol/kg of Gd-DTPA. Twenty-three of the 26 (88%) hepatocellular carcinomas showed total hyperintense enhancement relative to surrounding liver parenchyma in the early phase, and isointense or total hypointense enhancement in the late phase. Eleven of 13 (85%) hemangiomas showed peripheral hyperintense enhancement in the early phase, and peripheral or total hyperintense enhancement in the late phase. Cholangiocellular carcinomas were enhanced gradually from the early to the late phase. Metastatic liver tumors showed doughnut-like ring enhancement in all 8 lesions in the early phase. We concluded that 3 DFT-FISP dynamic MR imaging was useful in the differential diagnosis of liver tumor.

Adult↗

Phylogenetic subtypes of human T-lymphotropic virus type I and their relations to the anthropological background.

Isolates of human T-lymphotropic virus type I (HTLV-I) were phylogenetically analyzed from native inhabitants in India and South America (Colombia and Chile) and from Ainu (regarded as pure Japanese descendants from the preagricultural "Jomon" period). Their genomes were partially sequenced together with isolates from Gabon in central Africa and from Ghana in West Africa. The phylogenetic tree was constructed from the sequence data obtained and those of previously reported HTLV-I isolates and simian T-lymphotropic virus type I (STLV-I) isolates. The heterogeneity of HTLV-I was recently recognized, and one major type, generally called the "cosmopolitan" type, contained Japanese, Caribbean, and West African isolates. The phylogenetic tree constructed in the present study has shown that this cosmopolitan type can be further grouped into three lineages (subtypes A, B, and C). Subtype A consists of some Caribbean, two South American, and some Japanese isolates, including that from the Ainu, in addition to an Indian isolate, and subtype B consists of other Japanese isolates in addition to another Indian isolate, suggesting that there might be at least two ancestral lineages of the Japanese HTLV-I. Subtype A implies a close connection of the Caribbean and South American natives with the Japanese and thereby a possible migration of the lineage to the American continent via Beringia in the Paleolithic era. Subtype C consists of the West African and other Caribbean isolates, indicating that not all but part of the Caribbean strains directly originated from West Africa probably during the period of slave trade. The tree also has shown that the HTLV-I isolate from Gabon in central Africa forms a cluster with STLV-I from a chimpanzee, suggesting a possible interspecies transmission between man and the chimpanzee in the past. No specific clustering was observed in the tree in relation to manifestations of the disease such as adult T-cell leukemia and HTLV-I-related neurological disorders. Thus, the topology of the phylogenetic tree reflects the movement of people carrying the virus in the past.

Adult↗

Intravenous extended infusion of recombinant human soluble thrombomodulin prevented tissue factor-induced disseminated intravascular coagulation in rats.

This study demonstrated that intravenous infusion of recombinant human soluble thrombomodulin (rhs-TM) could inhibit disseminated intravascular coagulation (DIC) caused by 4 hr infusion of tissue factor (TF) in rats. Extended infusion of TF reduced fibrinogen and platelet counts and elevated serum FDP level. Pretreatment and coinfusion of rhs-TM could block changes of these DIC-parameters without prolongation of APTT. Heparin, which is a potent anti-DIC drug, could also inhibit these changes with extra prolongation of APTT and PT. Thus, these results suggest thrombomodulin prevent DIC less bleeding tendency than heparin.

Animals↗

Antithrombotic effects of recombinant human soluble thrombomodulin (rhs-TM) on arteriovenous shunt thrombosis in rats.

We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs-TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs-TM (0.5-4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose-dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25-200 U/kg) and in those treated with rhs-TM (0.5-4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs-TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs-TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs-TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis.

Animals↗

Induction of differentiation by radiation and hyperthermia in neuroblastoma-glioma hybrid cells.

The effects of either radiation or hyperthermia on the differentiation potential of NG108-15, a neuroblastoma-glioma hybrid cell line, were studied. After radiation and hyperthermia, the outgrowth of neurites from NG108-15 cells was potentiated, and polarizing current and voltage pulses induced a distinct action potential and a diphasic (inward following outward) current, respectively. An increase in the specific activity of acetylcholinesterase was also observed. In addition, both treatments induced an elevation of the concentration of intracellular calcium in some cells. The increase in intracellular calcium concentration caused by applying the calcium ionophore, A23187, induced differentiation. It is suggested that both the radiation- and the hyperthermia-induced increases of electrical excitability and acetylcholinesterase activity may have originated from an increase in intracellular Ca2+ concentration.

Acetylcholinesterase↗

Enhancement of murine serum amyloid A3 mRNA expression by glucocorticoids and its regulation by cytokines.

Macrophages are regulated by hormones, cytokines, and other substances. We examined the effects of glucocorticoids (GC) on serum amyloid A (SAA) mRNA expression using an antisense SAA3 probe, and found that dexamethasone (DEX) and triamcinolone (TC) increased SAA3 mRNA expression by macrophage cell lines in a time- and concentration-dependent manner. Both an RNA polymerase II antagonist, alpha-amanitin, and a specific GC antagonist, RU38486, inhibited the enhancement of SAA3 mRNA expression by DEX. These results show that GC lead to enhanced SAA3 mRNA transcription. Nuclear run-on experiments supported these results. Enhanced expression of SAA3 mRNA by DEX was accompanied by production of SAA3 protein. Interferon-gamma (IFN-gamma) alone showed any effect on SAA3 mRNA expression. Enhanced SAA3 expression by DEX was inhibited by treatment with IFN-gamma in a dose-dependent manner. Either transforming growth factor (TGF)-beta 1 or interleukin (IL)-4 alone showed no effect on SAA3 mRNA expression, but suppressed DEX-induced SAA3 expression. The timing of the effects of IFN-gamma and TGF-beta 1 on DEX-induced SAA3 expression differed: IFN-gamma showed its effect between 30 h before and 18 h after DEX administration, whereas TGF-beta 1 showed an effect when administered concomitantly with DEX and in the late stages after DEX administration. IL-4 mildly suppressed DEX-induced SAA3 expression when given 12 h before and after DEX administration.

Animals↗

Skip mediastinal lymph node metastasis in non-small cell lung cancer.

We retrospectively investigated 186 non-small cell lung cancer cases with N2 disease in order to clarify the significance of skip metastasis. Of the 186 patients with N2 disease, negative N1 nodes recognized to be skip metastasis were seen in 62 patients (33%). The incidence of skip metastasis was not statistically different regarding histology, T status, or M status. The incidence of the skip metastatic site consisted of 35 cases (56%) at sites 1, 2 and 3, while 8 cases (13%) were found at sites 8 and 9. Among the patients with right lung cancer, the skip metastatic incidence for site 7 (subcarinal) was higher in patients with either middle lobe or lower lobe cancer than in those with upper lobe cancer (P < 0.05). The 5-year survival rates of all N2 patients in comparison to those with skip metastasis were 22% and 24%, respectively. When the sites of mediastinal lymph nodes were classified as superior, aortic, and inferior, the 5-year survival rates of the patients with superior skip metastasis, aortic metastasis, and inferior metastasis were 23%, 36%, and 15%, respectively. No statistical difference was observed. The 5-year survival rate of the skip N2 patients with only aortic region involvement was 50% (n = 7). However, no statistically significant difference was found between the two groups (P = 0.08). Our results thus suggested that mediastinal involvement for the aortic region alone might have a better prognosis than the others. We thus conclude that a dissection of the complete hilar and mediastinal lymph nodes should be the procedure of choice in standard operations for non-small cell lung cancer because of the high frequency of skip metastasis.

Adult↗

X-ray crystal structure and molecular dynamics simulation of bovine pancreas phospholipase A2-n-dodecylphosphorylcholine complex.

The crystal structure of n-dodecylphosphorylcholine (n-C12PC)-bovine pancreas phospholipase A2 (PLA2) complex provided the following structural characteristics: (1) the dodecyl chain of n-C12PC was located at the PLA2 N-terminal helical region by hydrophobic interactions, which corresponds to the binding pocket of 2-acyl fatty acid chain (beta-chain) of the substrate phospholipid, (2) the region from Lys-53 to Lys-56 creates a choline-receiving pocket of n-C12PC and (3) the N-terminal group of Ala-1 shifts significantly toward the Tyr-52 OH group by the binding of the n-C12PC inhibitor. Since the accuracy of the X-ray analysis (R = 0.275 at 2.3 A resolution) was insufficient to establish these important X-ray insights, the complex structure was further investigated through the molecular dynamics (MD) simulation, assuming a system in aqueous solution at 310K. The MD simulation covering 176 ps showed that the structural characteristics observed by X-ray analysis are intrinsic and also stable in the dynamic state. Furthermore, the MD simulation made clear that the PLA2 binding pocket is large enough to permit the conformational fluctuation of the n-C12PC hydrocarbon chain.

Animals↗

Preparation and clinical evaluation of technetium-99m dimercaptosuccinic acid for tumour scintigraphy.

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. 99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO3 solution in the presence of a small amount of reducing agent (SnCl2). On the other hand, trivalent 99mTc-DMSA [99mTc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only 99mTc(V)-DMSA revealed an area of intense accumulation.

3-Iodobenzylguanidine↗

Primary leiomyosarcoma or leiomyoma of the pubic bone? A case report.

We report a case of what appeared to be a primary leiomyosarcoma of the left pubic bone of a female aged 23 years. Forty-eight cases of the tumour have been recorded in the literature since 1944, only two of which were in the pelvis. The tumour in our patient was treated by curettage and there was no recurrence in the following 3 years. The tumour cells showed only mild cellular atypism and 2 to 3 mitoses per 10 high-power fields. These finding suggest that the tumour might be an extremely rare leiomyoma of bone.

Adult↗

Three-dimensional architecture of the tubular endocytic apparatus and paramembranous networks of the endoplasmic reticulum in the rat visceral yolk-sac endoderm.

The three-dimensional architecture of the tubular endocytic apparatus and the endoplasmic reticulum in the rat yolk-sac endoderm was investigated after loading with horseradish peroxidase-conjugated concanavalin A by intrauterine administration. After 30 min, small vesicles (50-150 nm in diameter), small tubules (80-100 nm in diameter) and large vacuoles (0.2-1.0 microns in diameter) in the apical cytoplasm were labeled with the tracer, but lysosomes (1.0-3.5 microns in diameter) in the supranuclear cytoplasm were not labeled until 60 min after loading. Stereo-viewing of the labeled small tubules in thick sections revealed that they were not isolated structures but formed three-dimensional anastomosing networks, which were also confirmed by scanning electron microscopy after maceration with diluted osmium tetroxide. Their earlier labeling with the endocytic tracer, localization in the apical cytoplasm and three-dimensional network formation indicated that the labeled small tubules represented tubular endosomes (tubular endocytic apparatus). These well-developed membranous networks provided by the tubular endosomes are suggested to facilitate the receptor-mediated endocytosis and transcytosis of the maternal immunoglobulin in the rat yolk-sac endoderm. Scanning electron microscopy further revealed lace-like networks of the smooth endoplasmic reticulum near the lateral plasma membrane. Their possible involvement in transport of small molecules or electrolytes is discussed.

Animals↗

Video thoracoscopic excision of an intercostal neurilemoma presenting as a lateral chest wall tumor.

Thoracoscopic surgery has expanded with advances in endoscopic surgical instrumentation. We report on a 21-year-old woman with a complete thoracoscopic resection of an intercostal neurilemoma, which occurred extrapleurally in the ninth intercostal space of the lateral thoracic wall. The tumor was 70 x 40 x 25 mm in size, but a thoracotomy with a rib resection was avoided. The patient had an uncomplicated postoperative course and was discharged on the fourth postoperative day. Thoracoscopic resection of an intercostal neurilemoma, presenting as a lateral chest wall tumor, may be a safe and useful approach with an improved cosmetic result.

Adult↗

Five-year survival after transcatheter chemoembolization for hepatocellular carcinoma.

The 5-year cumulative survival rate of 443 patients who underwent transcatheter chemoembolization (TCE) for non-resectable hepatocellular carcinoma (HCC) before December 1986 was 8.0%, and 29 patients survived for 5 years or more. Of these 29 patients, 25 were men and 4 were women; their mean age was 63.9 years. Macroscopic classification showed lesions of the single nodular type in 16 cases, the multiple nodular type in 10 cases, and the massive type in 3 cases; 12 of the single nodular lesions measured 5 cm or less in size. The TNM classification showed lesions of stage I in 3 cases, stage II in 14 cases, stage III in 6 cases, and stage IV in 6 cases. Lesions classified as Child A were found in 23 patients, and they were thus much more common than Child B lesions (2 patients) and Child C lesions (1 patient). The response was analyzed in relation to the use of iodized oil (Lipiodol). It was used in 215 of the patients, and the 5-year cumulative survival rate of those patients was 12.9% (23 of them survived for 5 years or more). Lipiodol was not used in 228 patients, and they showed a 5-year cumulative survival rate of 3.4%, with 6 patients surviving for 5 years or more. The 6 patients with stage III disease and the 6 with stage IV disease received Lipiodol. TCE with Lipiodol thus contributed greatly in prolonging the survival of patients with HCC complicated by intrahepatic metastases or intraportal tumor thrombi.

Adult↗

Chondroid chordoma versus low-grade chondrosarcoma of the base of the skull: can immunohistochemistry resolve the controversy?

The classification of cartilaginous tumors of the skull base, including chondroid chordoma and chondrosarcoma remains the subject of controversy. Critical review of the literature and our own experience of chordomas and cartilaginous tumors of the skull base led to the following conclusions: 1) Chondrosarcoma of the skull base is a distinct clinicopathological entity. The immunohistochemical staining pattern (cytokeratin negative, epithelial membrane antigen (EMA) negative) can be helpful in distinguishing it from chordoma with chondroid differentiation (cytokeratin positive, EMA positive). 2) The chondroid chordomas originally described by Heffelfinger et al. may have included some true chondrosarcomas with focal areas of myxoid chordomalike appearance. 3) Focal chondroid differentiation in chordoma is not such a rare phenomenon. Further study is needed to define whether chordoma with chondroid foci should be separated out from conventional chordoma as a distinct entity with a better prognosis.

Adolescent↗

Cystic angiomatosis of bone with sclerotic changes mimicking osteoblastic metastases.

Five unusual cases of cystic angiomatosis of bone which presented with the radiologic appearance of osteoblastic lesions are reported. Three patients were female (ages 37, 41, and 65 years) and two were male (ages 24 and 66 years). Although cystic angiomatosis of bone usually produces widespread osteolytic lesions with a honeycombed appearance in the skeletal system, multiple osteoblastic lesions mimicking metastatic osteoblastic carcinoma are sometimes seen. This radiological presentation has not been well emphasized in previous reports. Histologically, in addition to the angiomatous lesions, both mature thickened lamellar bone trabeculae and immature trabeculae of woven bone were found. In one of our patients, increasing density of the osteoblastic lesions was noted over time. One previous study has suggested that the age of the lesions of cystic angiomatosis is related to radiographic density. It is important to recognize this uncommon variant of cystic angiomatosis and to include this entity among the radiologic differential diagnoses when multiple osteoblastic lesions are encountered.

Adult↗

Changing practices in the surgical treatment of breast cancer in Japan: a nationwide survey by the Japanese Breast Cancer Society.

A nationwide survey in Japan of the patients with primary breast cancer from 1989 to 1991 revealed marked changes in the surgical treatment of the disease. During this period, there was a significant trend toward fewer instances of radical and extended radical mastectomies, and an increase in modified radical mastectomies and breast-conserving surgery. The percentage of breast-conserving surgery for the early-stage disease increased from 6.8% to 12.7%. Among the types of operations for breast-conserving surgery, quadrantectomy was used for 51.5% of the cases, while either a partial mastectomy or a subcutaneous mastectomy was used for 18.2% and 18.9%, respectively; a lumpectomy was performed in 10.9% of the cases. As for the proportion of patients receiving radiation therapy after breast-conserving surgery, 77% of those undergoing lumpectomy received radiation, in contrast to only 43% of the patients undergoing quadrantectomy. According to the data from 1991, we also found that breast-conserving surgery was performed more often in larger cities and urban areas in Japan. As a result, we found that substantial changes in the treatment of localized breast cancer had taken place from 1989 to 1991. Regarding the details of breast-conserving surgery, however, some variation still remains in spite of the publication of numerous clinical trials.

Breast Neoplasms↗